Abstract: Esophageal squamous cell neoplasia (ESCN) is the sixth leading cause of cancer death worldwide with only 1 in 5 patients surviving three or more years due to diagnosis at an advanced stage. When detected early, endoscopic treatment can be performed resulting in dramatically improved survival (>90%). Unfortunately, early neoplasia is difficult to visualize on routine white light endoscopy. Pre-cancerous lesions and carcinoma often appear as small erosions, flat lesions, or normal mucosa and recognition of neoplasia is difficult even for experienced endoscopists. Currently, endoscopic screening is performed in high-risk patients using Lugol's chromoendoscopy (LCE). Although LCE increases sensitivity to >95%, specificity remains <65%, resulting in many unnecessary biopsies and increased cost. Recent studies have shown that Narrow-Band Imaging with magnification has significantly higher positive predictive value compared to LCE. However, it has proven difficult to implement any esophageal screening programs in low-resource settings due to the high cost of conventional endoscopy equipment (>$40,000), the need to sedate patients undergoing conventional endoscopy, and the lack of infrastructure to process equipment and biopsies. Capsule endoscopy is an attractive alternative for low-resource settings because patients do not require sedation. However, current capsule endoscopy systems lack sensitivity to diagnose ESCN because of limited spatial resolution; moreover, commercially available capsule endoscopy systems are expensive ($25,000). The goal of this proposal is to develop a $2,500 high-resolution capsule endoscopy system to allow less experienced providers to screen for ESCN in low resource settings. The system has two components: a reusable, $50 tethered capsule that is swallowed to collect images of the mucosa and supporting hardware to manipulate and display the collected data on a tablet computer. The system is named ScanCap because the tether causes the capsule to rotate as it descends through the esophagus during peristalsis so that it captures high resolution images from the entire esophagus. The system is portable, battery operated and designed for use by non-physicians in underserved settings. The system is designed to acquire high definition images to enable visualization of capillary loops; this is a significant advantage to current, untethered ?PillCam? systems. Here, we aim to: (1) design and fabricate the ScanCap components; (2) integrate the ScanCap components and develop a tablet computer control system to display and review images; (3) evaluate performance of ScanCap in the lab and in the oral mucosa of volunteers; and (4) compare performance of ScanCap and conventional endoscopy using resected patient samples. Our multi-disciplinary team will leverage advances in consumer grade image sensors, injection molded lenses, and optical scanner technology to design a reusable capsule that rivals the performance of high-definition chromoendoscopy systems used in the US. This makes the project both high-risk, but also a game changer for the global future of esophageal endoscopy.